Some Clinical Observations on the Treatment with L-Asparaginase of the Acute Leukemias

Abstract

The history of this new type of enzymatic depletion of the amino acid asparagine, which has been shown to be indispensable for the growth most particularly of the early cellular stages of the lymphatic system and, to a lesser degree, of some other tissues, has passed through several distinct investigational phases. The first stage was, characteristically, purely biological, starting with Clementi’s [17] preliminary report in 1922 of the richness in asparaginase of guinea pig serum, comprising Kidd’s [30] pioneering observations in 1953 on the suppression of certain transplanted lymphomas of mice and rats by guinea pig serum and finally including Broome’s [13] experimental demonstration that the enzyme L-asparaginase (L-ase) was the growth-inhibitory fraction of guinea pig serum, a finding later confirmed by the demonstration by Mashburn and Wriston [34] that L-ase derived from Escherichia coli had the same effect as that from guinea pig serum. This important discovery, together with the additional demonstration that L-ase derived from E. coli exists in two forms, known as EC-1 and EC-2 [16], of which only the second was active against 6C3HED lymphoma in mice [39, 40], opened up the possibility of large-scale production for clinical trials.